Epileptiform Discharges Drive High-frequency Oscillations Within the Retrosplenial Cortex of Mice with Third Trimester Alcohol Exposure

Abstract

Fetal Alcohol Spectrum Disorders (FASDs) are associated with alterations in learning and memory that persist throughout the lifespan. Thus, determining the neural mechanisms driving these alterations has the potential to identify novel therapeutic targets for improving memory in those with FASD. Given the newly realized role of the Retrosplenial cortex (RSC) for learning and memory, as well as the profound neural apoptosis that exposure to alcohol during development causes to this brain region, we recorded electrophysiological activity from mice exposed to alcohol during the third trimester-equivalent developmental time period. We observed a large number of Epileptiform Discharges (EDs) in alcohol-exposed subjects compared to controls, which were found to drive with High-frequency Oscillations (HFOs). Furthermore, many features of HFOs (amplitude/duration/etc.) were found to be directly proportional to the temporal distance from ED onset. These findings identify EDs for the first time as a critical feature in a preclinical model of FASD, and suggest their relationship to RSC HFOs may be a key mechanism driving memory alterations.